Retinol (vitamin A) is an endogenous compound which occurs naturally in the human body and is essential for normal epithelial cell differentiation. Natural and synthetic vitamin A derivatives have been used extensively in the treatment of a variety of skin disorders and have been used as skin repair or renewal agents. Retinoic acid has been employed to treat a variety of skin conditions, e.g., acne, wrinkles, psoriasis, age spots and discoloration. See e.g., Vahlquist, A. et al., J. Invest. Dermatol., Vol. 94, Holland D. B. and Cunliffe, W. J. (1990), pp. 496-498; Ellis, C. N. et al., "Pharmacology of Retinols in Skin", Vasel, Karger, Vol. 3, (1989), pp. 249-252; Lowe, N. J. et al., "Pharmacology of Retinols in Skin", Vol. 3, (1989), pp. 240-248; PCT Patent Application No. WO 93/19743. It is believed that the use of retinol or esters of retinol would be preferred over retinoic acid. Retinol is an endogenous compound which occurs naturally in the human body and is essential for normal epithelial cell differentiation. Retinol is also considered much safer than retinoic acid. Esters of retinol hydrolyze in-vivo to produce retinol. retinol and retinyl esters are considered ,safer than retinoic acid. Unfortunately, retinol and retinyl esters are less effective than retinoic acid at providing skin benefits.
The present invention is based, in part, on the discovery that a combination of retinol or retinyl esters with specific flavonoids results in a synergistic inhibition in keratinocyte differentiation. The effects of the flavonoids (specifically, naringenin and quercetin) combined with retinol or a retinyl ester were analogous to the effects of retinoic acid. Thus, a mixture of the specific flavonoids with retinol or retinyl esters mimics retinoic acid yet is easier and safer to use than retinoic acid.
Naringenin belongs to a subclass of flavonoids known as "flavonones". Quercetin belongs to a subclass known as "flavonols". Flavonones and flavonols are generally recognized as safe molecules and are sub-classes of a family of flavonoids. The term "flavonoids" represents a very large group of compounds consisting of two aromatic rings joined by a three carbon unit, (e.g., C.sub.6 --C.sub.3 --C.sub.6). The family of flavonoids includes monomeric flavonols, catechins, epicatechins (e.g., laurones), leucoanthocyanidins, proanthocyanidins, anthocyanidins, flavones, flavonones, chalcones, isoflavones, and neoflavones. Flavonoids are ubiquitous in plants. Although flavonoids do not seem to be of vital importance to the human diet, we consume flavonoids daily in fruits, vegetables, wine, cereals, drinks and food colorings.
Since the flavonoids are phenolic compounds, they act as potent antioxidants.
Cosmetic compositions employing flavonoids, in general, as antioxidants, are known. U.S. Pat. No. 5,431,912 (Nguyen et al.) discloses a cosmetic composition containing an amino acid lauroyl methionate and flavonoids (including naringenin and quercetin) to inhibit free radical formation. Compositions may also include .beta.-carotene (precursor of retinol). FR 2 687 572A discloses certain flavonoids (including naringenin) for protection of skin from singlet oxygen. .beta.-carotene or derivatives thereof may also be included. Meadowsweet extract containing flavonoids as radical scavengers is disclosed in the abstract of EP 0 507 035. U.S. Pat. No. 4,297,348 (Frazier) discloses a composition and method for the treatment of acne with naringin and naringenin. These documents do not appear to disclose naringenin or quercetin in combination with retinol or retinyl esters, or the ability of such combinations to mimic the effect of retinoic acid.
The art cited above does not disclose skin conditioning compositions based on synergistic combinations of naringenin or quercetin with retinol or a retinyl ester. None of the art cited above addresses the need for an effective alternative to retinoic acid.